Gonorrhea is the second most prevalent bacterial sexually transmitted infection globally and remains an important clinical and public health problem throughout the world. Gonococcal infections following sexual and perinatal transmission are a major source of morbidity worldwide [Barry, 2009]. Infections can involve cervicitis, proctitis, urethritis, pelvic inflammatory disease, epididymitis, orchitis, prostatitis, conjunctivitis, pharyngitis and other disseminated gonococcal diseases.
Neisseria gonorrhoeae, also known as gonococci (plural), GC (an abbreviation) or gonococcus (singular), is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.[1]
Complications include infertility, ectopic pregnancy, chronic pelvic pain, adverse outcomes of pregnancy, and increased susceptibility to and transmission of human immunodeficiency virus [Workowski, 2008; Barry, 2009].
Infections due to Chlamydia trachomatis and Neisseria gonorrhoeae can cause cervicitis, urethritis, proctitis, and pelvic inflammatory disease (PID), and their complications can significantly compromise a woman's reproductive functioning. These infections are a leading preventable cause of involuntary infertility and ectopic pregnancy and can influence pregnancy outcomes ranging from low birth weight, prematurity, fetal demise, and congenital infection. Chlamydial and gonococcal infections can also increase susceptibility to and facilitate transmission of HIV. Kimberly Workowski. 2013 American College of Physicians, Annals of Internal Medicine, In the Clinic.
A variety of antimicrobial agents have been used over the years for the treatment of gonorrhea; however, effective treatment options for gonorrhea have diminished rapidly because of the emergence and worldwide spread of antimicrobial resistance to many drugs previously used or considered first line, i.e., penicillins, narrow-spectrum cephalosporins, tetracyclines, macrolides, and fluoroquinolones [Workowski, 2008; Barry, 2009].
The current Centers for Disease Control and Prevention (CDC) recommended treatment regimen for uncomplicated gonorrhea is combination therapy with a single intramuscular dose of ceftriaxone plus either a single dose of azithromycin or a 7-day regimen of doxycycline [CDC, 2012]. While the CDC guidelines may help delay the emergence of cephalosporin-resistant gonorrhea, they are not able to eliminate this impending threat.
Therefore, the CDC has urged scientists and private-sector drug developers to prioritize the identification and study of new, effective antibiotic treatment options for gonorrhea [CDC, 2013].
WO02/08224, WO02/50061, WO02/56882, WO02/96907, WO2003087098, WO2003010138, WO2003064421, WO2003064431, WO2004002992, WO2004002490, WO2004014361, WO2004041210, WO2004096982, WO2002050036, WO2004058144, WO2004087145, WO2006002047, WO2006014580, WO2006010040, WO2006017326, WO2006012396, WO2006017468, WO2006020561, WO2006081179, WO2006081264, WO2006081289, WO2006081178, WO2006081182, WO01/25227, WO02/40474, WO02/07572, WO2004024712, WO2004024713, WO2004035569, WO2004087647, WO2004089947, WO2005016916, WO2005097781, WO2006010831, WO2006021448, WO2006032466, WO2006038172, WO2006046552, WO06099884, WO06126171, WO06137485, WO06105289, WO06125974, WO06134378, WO07016610, WO07081597, WO07071936, WO07115947, WO07118130, WO07122258, WO08006648, WO08003690 and WO08009700 disclose quinoline, naphthyridine, morpholine, cyclohexane, piperidine and piperazine derivatives having antibacterial activity. WO2004104000 discloses tricyclic condensed ring compounds capable of selectively acting on cannabinoid receptors. WO2003048081, WO2003048158 and US2003232804 disclose glycinamides as Factor Xa inhibitors.